Incorporation of second coordination sphere D-amino acids alters Cd(II) geometries in designed thiolate-rich proteins.

ABSTRACT: We use a de Novo protein design strategy to demonstrate that the second coordination sphere of a metal site plays a key role in controlling coordination geometries of Cd(II)-tris-thiolate complexes. Specifically, we show that alteration of chirality within the core hydrophobic packing region of a three-stranded coiled coil (3SCC) can control the coordination number of Cd(II) by limiting steric encumbrance to the metal center. Within a specific class of 3SCCs [Ac-G-(LKALEEK) _n -G-NH₂], where n = 4 is TRI and n = 5 is GRAND, one L-Leu may be substituted by L-Cys to generate a planar tris-thiolate array capable of metal binding. In the native peptide containing only the L-configuration of leucine, the three-Cys ligand site leads to a mixture of 3- and 4-coordinate Cd(II)

SUBMITTER: Ruckthong L 

PROVIDER: S-EPMC5756694 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature